We analyse the possibility that, in two Higgs doublet models, one or more of the Higgs couplings to fermions or to gauge bosons change sign, relative to the respective Higgs Standard Model couplings. Possible sign changes in the coupling of a neutral scalar to charged ones are also discussed. These wrong signs can have important physical consequences, manifesting themselves in Higgs production via gluon fusion or Higgs decay into two gluons or into two photons. We consider all possible wrong sign scenarios, and also the symmetric limit, in all possible Yukawa implementations of the two Higgs doublet model, in two different possibilities: the observed Higgs boson is the lightest CP-even scalar, or the heaviest one. We also analyse thoroughly the impact of the currently available LHC data on such scenarios. With all 8 TeV data analysed, all wrong sign scenarios are allowed in all Yukawa types, even at the 1 sigma level. However, we will show that B-physics constraints are crucial in excluding the possibility of wrong sign scenarios in the case where tan beta is below 1. We will also discuss the future prospects for probing the wrong sign scenarios at the next LHC run. Finally we will present a scenario where the alignment limit could be excluded due to non-decoupling in the case where the heavy CP-even Higgs is the one discovered at the LHC.